Water degradable film containing hyaluronic acid or salt thereof and polyphenol compounds

ABSTRACT

The present invention relates to a water degradable film comprising hyaluronic acid or a salt thereof and polyphenol compounds. The film of the present invention can transcribe nanofilms in the form of CNT (carbon nanotube), graphene and magnetic particles to various places. The film of the present invention can be dissolved by an aqueous solution or body fluid, and can be effectively used in the medical field since it is non-toxic and biocompatible. The film of the present invention can also be effectively used as a transcript that does not degrade the quality and performance of the device because no residue remains in the electronic device and the existing photolithography process.

CROSS-REFERENCES TO RELATED APPLICATION

This patent application claims the benefit of priority under 35 U.S.C. §119 from Korean Patent Application No. 10-2019-0111716 filed on Sep. 9,2019, the contents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention relates to a water degradable film, particularlyto a water degradable film comprising hyaluronic acid or a salt thereofand polyphenol compounds.

2. Description of the Related Art

The interest in biodegradable polymers is increasing day by day due tothe desire for life extension, increased interest in the environment,pollution problems of synthetic plastics, and increased demand forartificial organs and medical materials. Accordingly, studies onbiocompatible and biodegradable polymers are being actively conducted,and these biodegradable polymers are divided into natural polymers andsynthetic polymers.

The biodegradable natural polymers include chitosan, hyaluronic acid,flurane, and dextran. Since these are natural polymers, they have fewside effects in the human body and each has its own advantages, buttheir physical properties are very weak, and it is difficult to achievea desired purpose by carrying a therapeutic drug alone.

Particularly, hyaluronic acid (HA) is a colorless, high viscositypolysaccharide in which glucuronic acid, a repeating unit, andN-acetylglucosamine are alternately combined, and is naturally producedin organisms. Hyaluronic acid is a part of the extracellular matrix andis used in various medical applications due to its properties as alubricant in joints, eyes, etc. Specifically, hyaluronic acidderivatives have been developed for various purposes, such aspost-surgical adhesion barriers, anti-wrinkle agents, cosmetic aids,joint function improvers, drug carriers and cell culture supports(Scaffold), and in particular, active research is being conducted onanti-wrinkle agents and cosmetic aids for commercial use. In addition,hyaluronic acid exhibits excellent biocompatibility and moisturizingeffect and excellent lubrication effect on physical friction, so it isoften used as a cosmetic additive.

However, since hyaluronic acid dissolves very quickly in aqueousenvironments or body fluids, its modification is essential for variousapplications. There are many types of modification methods. For example,there is a method for producing a soluble form of hyaluronic acidderivatized with tyramine, which forms an insoluble hydrogel networkupon addition of a cross-linking agent. In addition, the solubility ofthe hyaluronic acid chain can be lowered by binding a hydrophobic groupthereto. Then, these derivatives become insoluble in the aqueous medium(depending on the molecular weight and the degree of substitution of thehydrophobic chain), and are generally soluble in mixtures of water andorganic solvents.

As one of the hyaluronic acid derivatives, the hyaluronic acidcross-linked product in which hyaluronic acids are cross-linked using across-linking agent has excellent biocompatibility, physical stability,and biodegradability. The hyaluronic acid cross-linked product can beprepared in various forms such as microbeads, seals, hydrogels, films,and sponges. But, the hyaluronic acid cross-linked product has arelatively low stability against hyaluronic acid degrading enzymes andheat, and it is difficult to remove non-reactive chemicals, so there isa limit to its use as a high purity biocompatible material.

In addition, the representative synthetic polymers with biodegradabilityinclude the U.S. FDA-approved poly(lactide) (PLA) and poly(glycolide)(PGA), and their copolymer poly(lactide-co-glycolide) (PLGA). Comparedto the natural polymers, the synthetic polymers have improved propertiesand are easy to carry therapeutic drugs, but lack the ability toselectively act on target cells or tissues, so they have problems ofaffecting normal cells or normal tissues.

On the other hand, in order to freely handle nanomaterials, especiallynanofilms (for example, 100 nm thick SWCNT film with magneticnanoparticles), there is a need for a technique to remove the nanofilmusing a tape and then move it to a desired location. For example, it isexpected that various applications will be possible if the nanofilm canbe detached using a 3M tape and attached it to the brain of a mouse.However, the 3M tape is a synthetic polymer that does not benefit anddoes not melt in the body.

Patent Reference 1 describes a self-supporting, biodegradable film basedon hydrophobized hyaluronic acid, a method of preparation and a usethereof. However, the film described in Patent Reference 1 cannot bedecomposed in and out of the body by moisture, and thus there is aproblem that is difficult to remove in vivo.

PRIOR ART REFERENCE Patent Reference

(Patent Reference 1) Korean Patent Publication No. 10-2017-0128351

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a water degradablefilm.

It is another object of the present invention to provide a waterdegradable film capable of transferring or transcribing nanomaterials.

It is another object of the present invention to provide a preparationmethod of a water degradable film capable of transferring ortranscribing nanomaterials.

It is another object of the present invention to provide a method fortransferring or transcribing nanomaterials.

To achieve the above objects, in an aspect of the present invention, thepresent invention provides a water degradable film comprising hyaluronicacid or a salt thereof and polyphenol compounds, wherein the polyphenolcompounds are interposed between at least a part of the polymer mainchains through hydrogen bonding.

In another aspect of the present invention, the present inventionprovides a water degradable film for transferring or transcribingnanomaterials comprising a nanomaterial; and a water degradable filmcomprising hyaluronic acid or a salt thereof and polyphenol compounds,wherein the polyphenol compounds are interposed between at least a partof the polymer main chains through hydrogen bonding.

In another aspect of the present invention, the present inventionprovides a preparation method of a water degradable film fortransferring or transcribing nanomaterials comprising the followingsteps:

preparing an aqueous solution by mixing hyaluronic acid or its salt andpolyphenol compounds in water (step 1);

applying the aqueous solution of step 1 on the substrate introduced withnanomaterials (step 2);

forming a film by drying the substrate of step 2 (step 3); and

separating the film prepared in step 3 from the substrate (step 4).

In another aspect of the present invention, the present inventionprovides a method for transferring or transcribing nanomaterialscomprising the following steps:

attaching the water degradable film for transferring or transcribingnanomaterials to a location where nanomaterials are to be introduced;and

decomposing and removing the film using water.

Advantageous Effect

The water degradable film comprising hyaluronic acid or a salt thereofand polyphenol compounds of the present invention can transcribenanofilms in the form of CNT (carbon nanotube), graphene and magneticparticles to various places. The film of the present invention can bedissolved by an aqueous solution or body fluid, and can be effectivelyused in the medical field since it is non-toxic and biocompatible. Thefilm of the present invention can also be effectively used as atranscript that does not degrade the quality and performance of thedevice because no residue remains in the electronic device and theexisting photolithography process.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram showing the water degradable film fortransferring or transcribing nanomaterials comprising a nanomaterial anda water degradable film, prepared on a silicon substrate.

FIG. 2a is a photograph showing the water degradable film comprising ahyaluronic acid polymer and tannic acid.

FIG. 2b is a photograph showing the water degradable film comprising ahyaluronic acid polymer and isoflavone.

FIG. 2c is a photograph showing the water degradable film comprising ahyaluronic acid polymer and catechin.

FIG. 2d is a photograph showing the water degradable film comprising ahyaluronic acid polymer and curcumin.

FIG. 3 is an image showing the water degradable film comprising ahyaluronic acid polymer and tannic acid, obtained by AFM (atomic forcemicroscopy).

FIG. 4 is a schematic diagram showing that the water degradable film isapplied on a CNT nanofilm introduced on a silicon wafer substrate.

FIG. 5a is a photograph showing the CNT nanofilm introduced on a siliconsubstrate.

FIG. 5b is a photograph showing the water degradable film fortransferring or transcribing nanomaterials attached to PDMS(polydimethylsiloxane) being decomposed by water, and the CNT nanofilmremaining on the PDMS.

FIG. 6a is a scanning electron microscope photograph showing theconventional bare CNT nanofilm.

FIG. 6b is a set of images showing the CNT nanofilm transferred to PDMS,obtained by AFM (atomic force microscopy).

FIG. 7 is a set of an image showing the edge of the CNT nanofilmtransferred to PDMS observed with AFM, and a graph showing theobservation results thereof.

FIG. 8a is a schematic diagram showing the preparation of a grapheneoxide nanofilm on a silicon substrate using a Langmuir-Blogetttechnique.

FIG. 8b is a photograph showing the preparation of a graphene oxidenanofilm on a silicon substrate using a Langmuir-Blogett technique.

FIG. 8c is a set of an image showing the graphene oxide nanofilmobserved with AFM (atomic force microscopy), and a graph showing theobservation results thereof.

FIG. 9a is a photograph showing the structure in which gold electrodesare deposited on the graphene oxide nanofilm.

FIG. 9b is a photograph showing the water degradable film fortransferring or transcribing nanomaterials prepared by applying thewater degradable film comprising a hyaluronic acid polymer and tannicacid on the structure prepared in FIG. 9 a.

FIG. 9c is a set of an image showing the graphene oxide film transferredto a silicon substrate after the water degradable film comprising ahyaluronic acid polymer and tannic acid was removed observed with AFM,and a graph showing the observation results thereof.

FIG. 10a is a photograph showing the film for transferring ortranscribing nanomaterials applied on cardiac muscle cells of a neonatalrat observed with an optical microscope.

FIG. 10b is a graph showing the results of analyzing the transferred CNTnanofilm by FT-Raman spectroscopy (Fourier Transform RamanSpectroscopy).

FIG. 10c is a photograph showing that the CNT nanofilm transferred tocardiac muscle cells of a neonatal rat, after the water degradable filmwas decomposed by water, is electrified.

FIG. 10d is a set of images showing the CNT nanofilm transferred tocardiac muscle cells of a neonatal rat observed with AFM.

FIG. 10e is a graph showing the results of observation of the CNTnanofilm transferred to cardiac muscle cells of a neonatal rat usingAFM.

FIG. 11a is a schematic diagram showing the photoresist (PR) linepattern formed on a silicon substrate.

FIG. 11b is an image showing the water degradable film remaining afterremoving the photoresist with acetone and applying the water degradablefilm for transferring or transcribing nanomaterials on the photoresistline pattern, observed with AFM.

FIG. 11c is a set of an image showing the remaining water degradablefilm observed with AFM, and a graph showing the observation resultsthereof.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Hereinafter, the present invention is described in detail.

In an aspect of the present invention, the present invention provides awater degradable film comprising hyaluronic acid or a salt thereof andpolyphenol compounds, wherein the polyphenol compounds are interposedbetween at least a part of the polymer main chains through hydrogenbonding.

The film can include the polyphenol compound in an amount of 0.05 to 10weight part, preferably 0.1 to 5 weight part, and more preferably 0.3 to1 weight part based on 1 weight part of hyaluronic acid or its salt.

The polyphenol compound can be one or more compounds selected from thegroup consisting of tannic acid, isoflavone, catechin, curcumin, tannin,hydroxy benzoic acid, hydroxy cinnamic acid, flavonoid, lignan,stilbene, caffeic acid, chlorogenic acid, anthocyan, pyrogallol, ellagicacid, gallic acid, theaflavin-3-gallate, resveratrol, kaempferol,quercetin, myricetin, luteolin, delphinidin, cyanidin, ampelopsin,hesperidin, aurantinidine, europinidin, pelargonidin, malvidin,peonidin, petunidin and rosinidin.

The film can be biodegradable.

Particularly, the film of the present invention uses hyaluronic acid anda polyphenol compound having high water solubility, so it can bedecomposed by an aqueous solution or moisture, body fluids, and thelike.

When the film of the present invention is applied to the medical field,it is easy to remove the film after transcribing (or transferring) thedesired nanomaterial in vivo or ex vivo. Therefore, it can be used as analternative for the conventional nanofilm. In addition, the film of thepresent invention can be used as a transcript for the transcription ofnanomaterials in the electronics industry, such as device processing aswell as the medical field.

The film can be prepared according to the preparation method of a waterdegradable film comprising the following steps:

preparing an aqueous solution by mixing hyaluronic acid or its salt andpolyphenol compounds in water (step 1);

applying the aqueous solution of step 1 on a substrate (step 2);

forming a film by drying the substrate of step 2 (step 3); and

separating the film prepared in step 3 from the substrate (step 4).

Hereinafter, the preparation method is described in detail.

Step 1 is a step of preparing an aqueous solution by adding anddissolving hyaluronic acid or its salt and polyphenol compounds inwater. At this time, the dissolution of step 1 can be performed bysonication, but not always limited thereto.

In step 1, a hyaluronic acid polymer having a molecular weight of 1.3 to1.8 Mda can be used, and tannic acid, isoflavone, catechin or curcumincan be used as a polyphenol compound, but not always limited thereto.

In addition, the polyphenol compound can be used in an amount of 0.05 to10 weight part, preferably 0.1 to 5 weight part, and more preferably 0.3to 1 weight part based on 1 weight part of hyaluronic acid or its salt.

Step 2 is a step of applying the aqueous solution on a substrate. Theapplication can be performed by a coating method. The coating method canbe one method selected from the group consisting of spin coating, dipcoating, roll coating, screen coating, spray coating, spin casting, flowcoating, screen printing, inkjet and drop casting. In an embodiment ofthe present invention, a solution was applied on a substrate accordingto a spin coating method, and then rotated at high speed to dry toprepare a water degradable film, but not always limited thereto.

Step 3 is a step of preparing a film by drying the solution coated onthe substrate. The drying can be performed using N₂ gas or on a hotplate in the range of 50 to 90° C., and the drying time is notparticularly limited, but is preferably 20 to 60 minutes.

Step 4 is a step of separating the dried film to finally obtain a film.

In another aspect of the present invention, the present inventionprovides a water degradable film for transferring or transcribingnanomaterials comprising a nanomaterial; and a water degradable filmcomprising hyaluronic acid or a salt thereof and polyphenol compounds,wherein the polyphenol compounds are interposed between at least a partof the polymer main chains through hydrogen bonding.

The nanomaterial can be one or more selected from the group consistingof nanowire, nanorod, nanosheet, nanoplate, nanosphere, nanotube,nanodiamond, nanofiber, nanoneedle, nanoparticle, and nanofilm.

The nanoparticle can be nanoparticle of any metal selected from thegroup consisting of platinum, aluminum, tin, lead, silver, copper, iron,cobalt, nickel, molybdenum, tungsten, selenium, tellurium, oxidesthereof, and combinations and alloys thereof; semiconductornanoparticle, magnetic nanoparticle, etc., but not always limitedthereto.

In an embodiment of the present invention, CNT nanofilm, graphenenanosheet, graphene oxide nanofilm, CNT nanofilm in which magneticnanoparticles are introduced, and the like were used, but not alwayslimited thereto.

In addition, a detailed description of the water degradable film of thewater degradable film for transferring or transcribing nanomaterials isthe same as the specific description of the water degradable film.

In an embodiment of the present invention, it was confirmed that thewater degradable film for transferring or transcribing nanomaterialstransferred the CNT nanofilm to PDMS without leaving residues. Thisindicates that the water degradable film for transferring ortranscribing nanomaterials of the present invention can be effectivelyused in the medical field or the electronics industry (see Example 1 andExperimental Example 1-1).

In an embodiment of the present invention, it was confirmed that thewater degradable film for transferring or transcribing nanomaterialstransferred the CNT nanofilm to cardiac muscle cells of a neonatal ratwithout residues. It was also confirmed that the transferred CNTnanofilm stimulated heart cells by applying electricity since it hadelectrical conductivity. These indicate that the water degradable filmfor transferring or transcribing nanomaterials of the present inventioncan be effectively used in the medical field (see Example 1 andExperimental Example 1-2).

In an embodiment of the present invention, it was confirmed that thewater degradable film for transferring or transcribing nanomaterialstransferred the graphene oxide nanofilm to the silicon substrate withoutresidues. It was also confirmed that several nanometer nanomaterialscould be handled through the water degradable film for transferring ortranscribing nanomaterials. These indicate that the water degradablefilm for transferring or transcribing nanomaterials of the presentinvention can be effectively used as a transcript in the electronicsindustry (see Example 1 and Experimental Example 2).

In an embodiment of the present invention, it was confirmed that thewater degradable film was not removed by acetone or an organic solventwhen the water degradable film for transferring or transcribingnanomaterials was attached on the photoresist line pattern and thephotoresist was removed with acetone in the photolithographic process.This means that the water degradable film attached line pattern wasformed. When another material to form a pattern on the water degradablefilm attached line pattern was coated and washed with water, the waterdegradable film was decomposed, and as a result, another materialpattern could be formed. That is, since the water degradable film fortransferring or transcribing nanomaterials of the present invention canbe applied to a photolithographic process to form patterns of variousmaterials, it can be effectively used in the electronics industry (seeExample 1 and Experimental Example 3).

In addition, the film of the present invention uses hyaluronic acid anda polyphenol compound having high water solubility, so it can bedecomposed by an aqueous solution or moisture, body fluids, and thelike.

When the film of the present invention is applied to the medical field,it is easy to remove the film after transcribing (or transferring) thedesired nanomaterial in vivo or ex vivo. In addition, the film of thepresent invention is biocompatible and has an effect that does not causeside effects, so it can be effectively used in the medical field. FIGS.10a-10e show the application examples for this.

The water degradable film for transferring or transcribing nanomaterialsof the present invention comprises hyaluronic acid or a salt thereof anda polyphenol compound, wherein the polyphenol compound is interposedbetween at least a part of the polymer main chains through hydrogenbonding. Since the nanomaterial is attached to the water degradablefilm, the film can be attached to the desired position to introduce thenanomaterial, and then the water degradable film is removed with waterto introduce the nanomaterial to the desired position. Therefore, thefilm of the present invention can be effectively used in the electronicsindustry, such as the manufacture of electronic devices. FIGS. 9a ˜9 cand 11 a˜11 c show the application examples for this.

Conventionally, it is well known to transcribe graphene using PMMA(Poly(methyl methacrylate)). But in this case, PMMA is not sufficientlywashed out with acetone, which degrades the quality of graphene anddegrades device performance.

On the other hand, the water degradable film for transferring ortranscribing nanomaterials of the present invention can be removed withan aqueous solution or water after attaching the nanomaterial to adesired position, so that the nanomaterial can be transcribed ortransferred without residues.

Therefore, the film of the present invention can be effectively used inthe electronics industry. In particular, when transferring the CNT andgraphene films in electronic device processes and photolithographyprocesses, the water degradable film for transferring or transcribingnanomaterials of the present invention can replace the photoresist andPMMA polymers.

In another aspect of the present invention, the present inventionprovides a preparation method of a water degradable film fortransferring or transcribing nanomaterials comprising the followingsteps:

preparing an aqueous solution by mixing hyaluronic acid or its salt andpolyphenol compounds in water (step 1);

applying the aqueous solution of step 1 on the substrate introduced withnanomaterials (step 2);

forming a film by drying the substrate of step 2 (step 3); and

separating the film prepared in step 3 from the substrate (step 4).

Hereinafter, the preparation method of the film is described in detail.

Step 1 is a step of preparing an aqueous solution by adding anddissolving hyaluronic acid or its salt and polyphenol compounds inwater. At this time, the dissolution of step 1 can be performed bysonication, but not always limited thereto.

In step 1, a hyaluronic acid polymer having a molecular weight of 1.3 to1.8 Mda can be used, and tannic acid, isoflavone, catechin or curcumincan be used as a polyphenol compound, but not always limited thereto.

In addition, the polyphenol compound can be used in an amount of 0.05 to10 weight part, preferably 0.1 to 5 weight part, and more preferably 0.3to 1 weight part based on 1 weight part of hyaluronic acid or its salt.

Step 2 is a step of applying the aqueous solution on a substrate. Theapplication can be performed by a coating method. The coating method canbe one method selected from the group consisting of spin coating, dipcoating, roll coating, screen coating, spray coating, spin casting, flowcoating, screen printing, inkjet and drop casting. In an embodiment ofthe present invention, a solution was applied on a substrate accordingto a spin coating method, and then rotated at high speed to dry toprepare a water degradable film, but not always limited thereto.

In addition, a detailed description of the nonmaterial is the same asthe specific description of the nonmaterial in the water degradable filmfor transferring or transcribing nanomaterials.

Step 3 is a step of preparing a film by drying the solution coated onthe substrate. The drying can be performed using N₂ gas or on a hotplate in the range of 50 to 90° C., and the drying time is notparticularly limited, but is preferably 20 to 60 minutes.

Step 4 is a step of separating the dried film to finally obtain a film.

In another aspect of the present invention, the present inventionprovides a method for transferring or transcribing nanomaterialscomprising the following steps:

attaching the water degradable film for transferring or transcribingnanomaterials to a location where nanomaterials are to be introduced;and

decomposing and removing the film using water.

Hereinafter, the present invention will be described in detail by thefollowing preparative examples, examples and experimental examples.

However, the following preparative examples, examples and experimentalexamples are only for illustrating the present invention, and thecontents of the present invention are not limited thereto.

Preparative Example 1: Preparation of CNT (Carbon Nanotube) Nanofilm

A CNT nanofilm that can be transcribed or transferred by the waterdegradable film for transferring or transcribing nanomaterials wasprepared as follows.

Step 1: Purification Process and Acid Treatment of CNT (Carbon Nanotube)

After adding 40 mg of a single wall carbon nanotube (ASP-100F, HanwhaChemical Co.) to a solution containing 10 ml of nitric acid and 30 ml ofsulfuric acid, ultrasonic treatment was performed for 4 hours to removethe metal catalyst present in the carbon nanotube. After filtering theacid treated carbon nanotube solution with an anodic aluminum oxidemembrane filter having a diameter of 200 nm, the filtered carbonnanotube was washed with tertiary distilled water to neutralize to pH 7.The washed carbon nanotube was dispersed in 250 ml of an aqueoussolution in which Triton X-100, a surfactant, was dispersed at theconcentration of 3 wt %, and then sonicated for 1 hour. Thereafter, toremove impurities such as a transition metal catalyst and amorphouscarbon, centrifugation was performed at 6000 rpm for 1 hour. Thesupernatant was taken to obtain an aqueous solution containing a carbonnanotube modified with a carboxyl group and a surfactant. The aqueoussolution was filtered with an anodic aluminum oxide membrane filter andthe surfactant was removed using 1 L of methanol, which was thendispersed in chloroform.

Step 2: Preparation of CNT Nanofilm by Filtration

4 ml of the carbon nanotube solution dispersed in chloroform prepared instep 1 (concentration: 0.1 mg/ml) was filtered with an anodic aluminumoxide membrane filter having a diameter of 200 nm to remove chloroform,and the carbon nanotube was laminated in the form of a network structureon the upper layer of the filter. The laminated carbon nanotube wasdried in an oven at 105° C. for 3 hours to vaporize the residualchloroform. A silicon wafer substrate was placed on the bottom of the 3Msodium hydroxide aqueous solution, and the carbon nanotube laminatedanodic aluminum oxide membrane filter was placed on the substrate for 4hours. The anodic aluminum oxide membrane was dissolved and removed bythe sodium hydroxide aqueous solution. Tertiary distilled water wasslowly added to the sodium hydroxide aqueous solution to neutralize thepH to 7, and the residual aqueous solution was removed using anaspirator while maintaining the pH at 7. As a result, a CNT (carbonnanotube) nanofilm introduced on a silicon wafer substrate was obtained(see FIG. 5a ).

Preparative Example 2: Preparation of Graphene Oxide Nanofilm

A grapheme oxide nanofilm that can be transcribed or transferred by thewater degradable film for transferring or transcribing nanomaterials wasprepared according to Langmuir-Blogett technique as follows.

A graphene oxide solution was prepared by adding 0.1 g of graphene oxideto 100 ml of tertiary distilled water and dissolving thereof byultrasonic treatment.

After mixing the solution (concentration: 1 mg/ml) with 4 ml ofmethanol, 200 μl of the mixed solution was applied dropwise to theLangmuir-Blodgett trough containing tertiary distilled water using amicro syringe dropwise, and the mixture was placed at room temperaturefor 30 minutes to vaporize methanol. Then, barriers on both sides of theLangmuir-Blodgett trough were collected at the speed of 4 mm/min. As aresult, a graphene oxide nanofilm was prepared as a thin film of uniformshape under the surface pressure of 13 mN/m (see FIGS. 8a ˜8 c).

Example 1: Preparation of Water Degradable Film Comprising Tannic Acid<1-1> Preparation of Water Degradable Film Comprising Hyaluronic AcidPolymer and Tannic Acid

To prepare a water degradable film, an aqueous solution in which ahyaluronic acid polymer and tannic acid were mixed was prepared.Particularly, 0.6 g of a hyaluronic acid polymer (molecular weight:1.3˜1.8 Mda) and 0.6 g of tannic acid (molecular weight: 1701.19 g/mol)were added to 30 ml of tertiary distilled water and dissolved byultrasonic treatment. As a result, an aqueous solution in which 4 wt %of a hyaluronic acid polymer and tannic acid were mixed was prepared.The chemical structures of the hyaluronic acid polymer and tannic acidused in the aqueous solution are shown below.

A water degradable film containing a hyaluronic acid polymer and tannicacid can be obtained by spin-coating the aqueous solution. When thewater degradable film was observed with an atomic force microscope (AFM)capable of viewing the nanostructure, the surface roughness (Rq) valuewas 0.367 nm, indicating that the water degradable film is very flat(see FIGS. 2a and 3).

<1-2> Preparation of Water Degradable Film for Transferring orTranscribing Nanomaterials Comprising Tannic Acid

The CNT (carbon nanotube) nanofilm prepared in Preparative Example 1 orthe graphene oxide nanofilm prepared in Preparative Example 2 was placedin a spin coater. 100 μl of the aqueous solution was dropped thereto,which was rotated at 3000 rpm for 30 seconds, followed by heat treatmentat 50° C. for 30 minutes using a heating stirrer. As a result, a waterdegradable film for transferring or transcribing nanomaterialscomprising a CNT (carbon nanotube) nanofilm or a graphene oxide nanofilmas a nanomaterial; and a water degradable film containing a hyaluronicacid polymer and tannic acid was prepared (see FIG. 4).

Example 2: Preparation of Water Degradable Film Comprising Isoflavone

To prepare a water degradable film, an aqueous solution in which ahyaluronic acid polymer and isoflavone were mixed was prepared.Particularly, 0.3 g of a hyaluronic acid polymer (molecular weight:1.3˜1.8 Mda) and 0.1 g of isoflavone (molecular weight: 222.24 g/mol)were added to 30 ml of tertiary distilled water and dissolved byultrasonic treatment. As a result, an aqueous solution in which 1.33 wt% of a hyaluronic acid polymer and isoflavone were mixed was prepared.The chemical structures of the hyaluronic acid polymer and isoflavoneused in the aqueous solution are shown below.

A PS (polystyrene) substrate was placed in a spin coater. 100 μl of theaqueous solution was dropped thereto, which was rotated at 3000 rpm for30 seconds, followed by heat treatment at 50° C. for 30 minutes using aheating stirrer. As a result, a water degradable film comprising ahyaluronic acid polymer and isoflavone was prepared (see FIG. 2b ).

Example 3: Preparation of Water Degradable Film Comprising Catechin

To prepare a water degradable film, an aqueous solution in which ahyaluronic acid polymer and catechin were mixed was prepared.Particularly, 0.3 g of a hyaluronic acid polymer (molecular weight:1.3˜1.8 Mda) and 0.1 g of catechin (molecular weight: 290.26 g/mol) wereadded to 30 ml of tertiary distilled water and dissolved by ultrasonictreatment. As a result, an aqueous solution in which 1.33 wt % of ahyaluronic acid polymer and catechin were mixed was prepared. Thechemical structures of the hyaluronic acid polymer and catechin used inthe aqueous solution are shown below.

A PS (polystyrene) substrate was placed in a spin coater. 100 μl of theaqueous solution was dropped thereto, which was rotated at 3000 rpm for30 seconds, followed by heat treatment at 50° C. for 30 minutes using aheating stirrer. As a result, a water degradable film comprising ahyaluronic acid polymer and catechin was prepared (see FIG. 2c ).

Example 4: Preparation of Water Degradable Film Comprising Curcumin

To prepare a water degradable film, an aqueous solution in which ahyaluronic acid polymer and curcumin were mixed was prepared.Particularly, 0.3 g of a hyaluronic acid polymer (molecular weight:1.3˜1.8 Mda) and 0.1 g of curcumin (molecular weight: 368.38 g/mol) wereadded to 30 ml of tertiary distilled water and dissolved by ultrasonictreatment. As a result, an aqueous solution in which 1.33 wt % of ahyaluronic acid polymer and curcumin were mixed was prepared. Thechemical structures of the hyaluronic acid polymer and curcumin used inthe aqueous solution are shown below.

A PS (polystyrene) substrate was placed in a spin coater. 100 μl of theaqueous solution was dropped thereto, which was rotated at 3000 rpm for30 seconds, followed by heat treatment at 50° C. for 30 minutes using aheating stirrer. As a result, a water degradable film comprising ahyaluronic acid polymer and curcumin was prepared (see FIG. 2d ).

Experimental Example 1: Transcription of CNT Nanofilm Using WaterDegradable Film for Transferring or Transcribing Nanomaterials

In order to confirm that the water degradable film for transferring ortranscribing nanomaterials according to the present invention has theeffect of transferring or transcribing nanomaterials, an experiment oftranscribing the CNT nanofilm to PDMS (polydimethylsiloxane) or cardiacmuscle cells of a neonatal rat was performed as follows. The results areshown in FIGS. 5a, 5b, 6a, 6b, and 10a ˜10 e.

<1-1> Transcription of CNT Nanofilm to PDMS (Polydimethylsiloxane)

The water degradable film for transferring or transcribing nanomaterialscomprising the CNT nanofilm prepared in Preparative Example 1; and awater degradable film containing a hyaluronic acid polymer and tannicacid was attached to PDMS (polydimethylsiloxane) and immersed indistilled water for 3 to 5 minutes. As a result, the water degradablefilm containing a hyaluronic acid polymer and tannic acid was decomposedby water, and the CNT nanofilm transferred to PDMS remained (see FIG. 5b). The images of the CNT nanofilm transferred to the PDMS observed withAFM (atomic force microscopy) were compared with the photographs ofscanning electron microscope of the conventional bare CNT. As a result,it was confirmed that the water degradable film containing a hyaluronicacid polymer and tannic acid was decomposed (see FIGS. 6a and 6b ). Inaddition, the edge portion of the CNT nanofilm transferred to PDMS wasobserved with AFM. As a result, the thickness of the CNT nanofilm wasabout 81 nm, and the edge portion was neatly formed, confirming that thewater degradable film was decomposed (see FIG. 7).

The results indicate that the water degradable film containinghyaluronic acid or its salt and polyphenol compound was dissolved anddisappeared by water in or out of the body, so that no residue remainedand the nanomaterial could be transferred to the desired place andremained. Therefore, it was confirmed that the water degradable film fortransferring or transcribing nanomaterials of the present invention canbe effectively used in the medical field or the electronics industry.

<1-2> Transcription of CNT Nanofilm to Neonatal Rat Cardiac Muscle Cells

Cardiac muscle cells of a neonatal rat were grown in a general cellculture container (TCPS, tissue culture polystyrene). The waterdegradable film for transferring or transcribing nanomaterialscomprising the CNT nanofilm prepared in Preparative Example 1; and awater degradable film containing a hyaluronic acid polymer and tannicacid was attached to the cardiac muscle cells, and immersed in distilledwater. As a result, the water degradable film containing a hyaluronicacid polymer and tannic acid was decomposed by water, and the CNTnanofilm transferred to the cardiac muscle cells (see FIG. 10a ).

The CNT nanofilm transferred to the cardiac muscle cells was observedwith AFM. As a result, it was confirmed that the cell flection of thecardiac muscle cells was about 427 nm deep, and that the waterdegradable film was decomposed without residues (see FIGS. 10d and 10e). In addition, the transferred CNT nanofilm was analyzed by FT-Ramanspectroscopy (Fourier Transform Raman Spectroscopy). As a result, Dband, G band, and G′ band, the Raman peaks, were 1350 cm⁻¹, 1573 cm⁻¹,and 2687 cm⁻¹, respectively, which are the characteristic Raman peaks ofthe CNT nanofilm. Therefore, it was confirmed that the CNT nanofilm wastransferred to the cardiac muscle cells (see FIG. 10b ). It was alsoconfirmed that electricity flows through the CNT nanofilm transferred tothe neonatal rat cardiac muscle cells (see FIG. 10c ).

The above results indicate that the water degradable film fortransferring or transcribing nanomaterials can transfer the nanomaterialto a highly curved portion such as a cell or a biological tissue withoutleaving residues. In addition, it shows that the CNT nanofilm haselectrical conductivity and can stimulate cardiac cells by applyingelectricity. Therefore, it was confirmed that the water degradable filmfor transferring or transcribing nanomaterials of the present inventioncan be effectively used in the medical field.

Experimental Example 2: Transcription of Grapheme Oxide Nanofilm UsingWater Degradable Film for Transferring or Transcribing Nanomaterials

In order to confirm that the water degradable film for transferring ortranscribing nanomaterials according to the present invention has theeffect of transferring or transcribing nanomaterials, an experiment oftransferring the graphene oxide nanofilm to a silicon substrate wasperformed as follows. The results are shown in FIGS. 9a ˜9 c.

Gold electrodes were deposited on the graphene oxide nanofilm preparedin Preparative Example 2. A water degradable film for transferring ortranscribing nanomaterials was prepared according to the method ofExample 1, except that the above structure was used (see FIGS. 9a and 9b). The film was attached to the silicon substrate, and immersed indistilled water. As a result, the water degradable film containing ahyaluronic acid polymer and tannic acid was decomposed by water, and thegraphene oxide nanofilm transferred to the silicon substrate. Thegraphene oxide nanofilm transferred to the silicon substrate wasobserved with AFM. As a result, it was confirmed that the thickness ofthe graphene oxide nanofilm was about 2 nm, and the water degradablefilm was decomposed without residues (see FIG. 9c ).

The above results indicate that the water degradable film containinghyaluronic acid or its and polyphenol compounds had excellent ability toseparate nanomaterials. After the water degradable film transferred ortranscribed the nanomaterial to the desired position, it was dissolvedand disappeared by water in or out of the body, so that no residueremained and the nanomaterial could be transferred to the desired place.Therefore, it was confirmed that the water degradable film fortransferring or transcribing nanomaterials of the present invention canbe effectively used in various industrial fields, especially in themedical field or the electronics industry field.

Experimental Example 3: Use of Water Degradable Film for Transferring orTranscribing Nanomaterials in Photolithography Process

In order to confirm whether the water degradable film for transferringor transcribing nanomaterials according to the present invention can beused in the photolithographic process, an experiment was performed asfollows. The results are shown in FIGS. 11a ˜11 c.

The water degradable film was attached on the photoresist (PR) linepattern formed on the silicon substrate, and the photoresist was removedwith acetone. As a result, it was confirmed that the water degradablefilm was not removed by acetone or an organic solvent. The waterdegradable film was observed with AFM. As a result, it was confirmedthat the water degradable film having a diameter of 25 μm and athickness of 100 nm remained not decomposed by acetone (see FIGS. 11a˜11 c).

This means that the water degradable film attached line pattern wasformed.

When another material to form a pattern on the water degradable filmattached line pattern was coated and washed with water, the waterdegradable film was decomposed, and as a result, another materialpattern could be formed.

That is, since the water degradable film for transferring ortranscribing nanomaterials of the present invention can be applied to aphotolithographic process to form patterns of various materials, it canbe effectively used in the electronics industry.

In the case of the conventional photoresist process, the photoresist isremoved using a toxic organic solvent, which is expensive in treatingwastewater and causes environmental pollution. In the photolithographyprocess, if the water degradable film for transferring or transcribingnanomaterials of the present invention is used instead of theconventional photoresist process, it is decomposed by an aqueoussolution, so that a toxic organic solvent may not be used, and it doesnot cause the above problems because it is environmentally friendly.Therefore, the water degradable film for transferring or transcribingnanomaterials of the present invention can be effectively used in theelectronics industry field such as the photolithography process.

BRIEF DESCRIPTION OF THE MARK OF DRAWINGS

-   -   1: silicon substrate    -   2: water degradable film    -   3: CNT nanofilm    -   4: graphene or graphene oxide film    -   5: magnetic nanoparticle    -   6: silicon substrate    -   7: water degradable film    -   8: CNT nanofilm    -   9: silicon substrate    -   10: CNT nanofilm    -   11: PDMS (polydimethylsiloxane)    -   12: CNT nanofilm    -   13: PDMS    -   14: CNT nanofilm    -   15: Langmuir-Blodgett trough    -   16: water face    -   17: graphene oxide film    -   18: barrier    -   19: Si (back gate)    -   20: SiO₂    -   21: photoresist (PR)

What is claimed is:
 1. A water degradable film comprising hyaluronicacid or a salt thereof and polyphenol compounds, wherein the polyphenolcompounds are interposed between at least a part of the hyaluronic acidmain chains through hydrogen bonding.
 2. The water degradable filmaccording to claim 1, wherein the film includes the polyphenol compoundin an amount of 0.05 to 10 weight part based on 1 weight part of thehyaluronic acid or its salt.
 3. The water degradable film according toclaim 1, wherein the polyphenol compound is one or more compoundsselected from the group consisting of tannic acid, isoflavone, catechin,curcumin, tannin, hydroxy benzoic acid, hydroxy cinnamic acid,flavonoid, lignan, stilbene, caffeic acid, chlorogenic acid, anthocyan,pyrogallol, ellagic acid, gallic acid, theaflavin-3-gallate,resveratrol, kaempferol, quercetin, myricetin, luteolin, delphinidin,cyanidin, ampelopsin, hesperidin, aurantinidine, europinidin,pelargonidin, malvidin, peonidin, petunidin and rosinidin.
 4. The waterdegradable film according to claim 1, wherein the film is characterizedin that it is biodegradable.
 5. A water degradable film for transferringor transcribing nanomaterials comprising a nanomaterial; and a waterdegradable film comprising hyaluronic acid or a salt thereof andpolyphenol compounds, wherein the polyphenol compounds are interposedbetween at least a part of the hyaluronic acid main chains throughhydrogen bonding.
 6. The water degradable film for transferring ortranscribing nanomaterials according to claim 5, wherein thenanomaterial is any one selected from the group consisting of nanowire,nanorod, nanosheet, nanoplate, nanosphere, nanotube, nanodiamond,nanofiber, nanoneedle, nanoparticle and nanofilm.
 7. A preparationmethod of a water degradable film for transferring or transcribingnanomaterials of claim 5 comprising the following steps: preparing anaqueous solution by mixing hyaluronic acid or its salt and polyphenolcompounds in water (step 1); applying the aqueous solution of step 1 onthe substrate introduced with nanomaterials (step 2); forming a film bydrying the substrate of step 2 (step 3); and separating the filmprepared in step 3 from the substrate (step 4).
 8. The preparationmethod according to claim 7, the polyphenol compound is mixed in anamount of 0.05 to 10 weight part based on 1 weight part of thehyaluronic acid or its salt in step
 1. 9. A method for transferring ortranscribing nanomaterials comprising the following steps: attaching thewater degradable film for transferring or transcribing nanomaterials ofclaim 5 to a location where nanomaterials are to be introduced; anddecomposing and removing the film using water.